Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model

Abstract

Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P < 0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P < 0.05), which were reduced in all the treatment groups (P < 0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P < 0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.

Cardiac cachexia: hic et nunc

“…At a daily dose of 10 mg/kg body weight, it attenuated the weight loss . Similar effects were observed in another experiment performed in the murine cancer cachexia model, where imidapril attenuated the muscle and adipose tissue depletion . Transfer to patients with cancer cachexia was already conducted in a randomized placebo controlled trial, but the findings were not published yet …”

“…75 Similar effects were observed in another experiment performed in the murine cancer cachexia model, where imidapril attenuated the muscle and adipose tissue depletion. 103 Transfer to patients with cancer cachexia was already conducted in a randomized placebo controlled trial, but the findings were not published yet. 104 Another attractive concept for prevention of body wasting is the exercise training that is expanding over a variety of chronic disease, including the cachexia patients.…”

l-Glutamine supplementation promotes an improved energetic balance in Walker-256 tumor–bearing rats

“…The development of a cancer leads to a loss of energy balance in response to the intensification of catabolism, which, in turn, results in cancer-associated cachexia. 1–13 The lower cachexia index and reduced body weight loss in WTG rats compared to the WT group confirmed our previous studies demonstrating the beneficial effects of l -glutamine supplementation in the diet, particularly in the small intestine. 33,37…”

“…One of the most marked negative effects of cancer is cachexia, a complex syndrome characterized by anorexia, and increased proteolysis with loss of muscle and adipose mass. 1–10 The prevalence of cachexia in gastric, pancreatic, lung, advanced colorectal, or prostate neoplasias is more than 50%, whereas it is estimated to be between 30% and 50% in non-Hodgkin lymphoma, breast cancer, sarcomas, and leukemias. 11 Moreover, a cachectic status worsens the prognosis and implies increased mortality, being responsible for the death of 22% of cancer patients.…”

Renin–Angiotensin System Inhibitors to Mitigate Cancer Treatment–Related Adverse Events

“…Several preclinical studies have demonstrated that ACEi can control cancer cachexia in different rodent models (13,105,106), while imidapril had no beneficial effect on cardiac wasting in a rat hepatoma cancer cachexia model (107). In a subcutaneous murine colon cancer model, the direct renin inhibitor aliskiren had potent anti-cachexia effects.…”